Hydrochloric Acid → N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(1-hydroxyethyl)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide

HRID 1874701Notes

Reaction equation

HRID 1874701 reaction equation
[BH4-].[Na+].CC([N:7]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][N:19]2[C:27]3[C:22](=[C:23]([C:28](=[O:30])[CH3:29])[CH:24]=[CH:25][CH:26]=3)[C:21]([NH:31][S:32]([C:35]3[S:36][C:37]([Cl:40])=[CH:38][CH:39]=3)(=[O:34])=[O:33])=[N:20]2)[CH:13]=1)C(=O)[O-])(C)C.Cl.O1CCOCC1>CO>[NH2:7][CH2:11][C:12]1[CH:13]=[C:14]([CH2:18][N:19]2[C:27]3[C:22](=[C:23]([CH:28]([OH:30])[CH3:29])[CH:24]=[CH:25][CH:26]=3)[C:21]([NH:31][S:32]([C:35]3[S:36][C:37]([Cl:40])=[CH:38][CH:39]=3)(=[O:34])=[O:33])=[N:20]2)[CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 4311764Sodium borohydrideHCID 866448151,1-dimethylethyl({3-[(4-acetyl-3-{[(5-chloro-2-thienyl)sulfonyl]amino}-1H-indazol-1-yl)methyl]phenyl}methyl)carbamate

Product 1

HCID 59456025N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(1-hydroxyethyl)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium borohydride (20.52 mg, 0.543 mmol) was added to a stirring solution of 1,1-dimethylethyl({3-[(4-acetyl-3-{[(5-chloro-2-thienyl)sulfonyl]amino}-1H-indazol-1-yl)methyl]phenyl}methyl)carbamate (for a preparation see Intermediate 75) (260 mg, 0.452 mmol) in MeOH (5 mL) at 25° C. under N2. The reaction mixture was stirred at room temp for 2 h. About ˜⅔ of the methanol was evaporated in vacuo and the residue was treated slowly with 1M HCl (5 mL). The product was extracted with EtOAc (2×40 mL) and the combined organic layers were dried by passing through a hydrophobic frit and concentrated to afford a yellow oil. 4N HCl in Dioxane (2 mL, 8.00 mmol) was added to the residue at 25° C. and the reaction mixture was stirred for 30 min. The crude sample was loaded straight on to a pre-washed (MeOH) SPE sulphonic acid (SCX-2) cartridge (20 g). The SCX cartridge was washed with 2 column volumes of MeOH and the product was collected by washing with 3 column volumes of 2N Ammonia in MeOH. The appropriate fractions were combined and evaporated in vacuo to give the title compound (235 mg, 91)%. LCMS (System A) RT=0.77 min, ES+ve m/z 477/479 (M+H)+.

Workup

  1. customat 25° C.
  2. customAbout ˜⅔ of the methanol was evaporated in vacuo
  3. additionthe residue was treated slowly with 1M HCl (5 mL)
  4. extractionThe product was extracted with EtOAc (2×40 mL)
  5. customthe combined organic layers were dried
  6. concentrationconcentrated
  7. customto afford a yellow oil
  8. stirringthe reaction mixture was stirred for 30 min
  9. washa pre-washed (MeOH) SPE sulphonic acid (SCX-2) cartridge (20 g)
  10. washThe SCX cartridge was washed with 2 column volumes of MeOH
  11. customthe product was collected
  12. washby washing with 3 column volumes of 2N Ammonia in MeOH
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-6330130bbcd24ea8b28ad660090fd2fa
Source dataset
uspto-grants-2012_11
Patent number
US08304446B2

Reaction notes

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